TY - JOUR
T1 - Epigenome-wide association study in hepatocellular carcinoma
T2 - Identification of stochastic epigenetic mutations through an innovative statistical approach
AU - Gentilini, Davide
AU - Scala, Stefania
AU - Gaudenzi, Germano
AU - Garagnani, Paolo
AU - Capri, Miriam
AU - Cescon, Matteo
AU - Grazi, Gian Luca
AU - Bacalini, Maria Giulia
AU - Pisoni, Serena
AU - Dicitore, Alessandra
AU - Circelli, Luisa
AU - Santagata, Sara
AU - Izzo, Francesco
AU - Di Blasio, Anna Maria
AU - Persani, Luca
AU - Franceschi, Claudio
AU - Vitale, Giovanni
PY - 2017/6/27
Y1 - 2017/6/27
N2 - Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided valuable clues for further investigations in understanding the process of tumorigenesis in HCC.
AB - Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade. A significant positive association emerged between SEMs measured in peritumoral tissue and hepatitis B and/or C virus infection status. A restricted number of SEMs resulted to be shared by more than 90% of HCC tumor samples and never present in peritumoral tissue. This analysis allowed the identification of four epigenetically regulated candidate genes (AJAP1, ADARB2, PTPRN2, SDK1), potentially involved in the pathogenesis of HCC.In conclusion, HCC showed a methylation profile completely deregulated and very far from adjacent non-cancerous liver tissues. The SEM analysis provided valuable clues for further investigations in understanding the process of tumorigenesis in HCC.
KW - Journal Article
U2 - 10.18632/oncotarget.17462
DO - 10.18632/oncotarget.17462
M3 - Article
C2 - 28514750
SN - 1949-2553
VL - 8
SP - 41890
EP - 41902
JO - Oncotarget
JF - Oncotarget
IS - 26
ER -